The present invention relates to a novel thrombolytic agent comprising, as an effective ingredient thereof, at least one protease selected from the group consisting of protease F-III-1-HM-27 (referred to as HM-27 hereinafter), protease F-III-2-HM-89 (referred to as HM-89 hereinafter), protease F-0-HM-45 (referred to as HM-45 hereinafter), protease F-I-1-HM-54 (referred to as HM-54 hereinafter), protease F-I-2-HM-15 (referred to as HM-15 hereinafter), protease F-II-HM-64 (referred to as HM-64 hereinafter), protease F-III.sup.1, protease F-II.sup.1, protease F-I.sup.1 and protease F-I.sup.2. Each of these proteases is a white amorphous powder obtained by purifying the extracted material from the tissues of earthworms belonging to the family of Lumbricidae such as Lumbricus rebellus and characterized by the activity of dissolving fibrin, i.e. fibrinolytic activity, and an activity of dissolving thrombi. Such an effective ingredient is not described in any prior art literatures.
Among the above named proteases, the HM-27, HM-89, HM-45, HM-54, HM-15 and HM-64 are each a purified protease of a single component while the proteases F-III.sup.1, F-II.sup.1, F-I.sup.1 and F-I.sup.2 are each a composite composed of two or three kinds of the above named single proteases. That is, protease F-III.sup.1 is a composite of HM-27 and HM-89, protease F-I.sup.1 is a composite of HM-54 and HM-15 and protease F-I.sup.2 is a composite of HM-45, HM-54 and HM-15. Protease F-II.sup.1 is a semi-purified protease mainly composed of HM-64.
These novel proteases can be obtained in a crude form by extracting earthworm tissues with an aqueous extractant solvent at a suitable temperature for a suitable length of time followed by, if necessary, keeping the extract solution for a suitable length of time at a suitable temperature or in a purified form by purifying the above obtained crude products in a known method.
In recent years, attention is directed by the practitioners of medicine and pharmaceutics to various types of the deseases due to the coagulation of blood occurring in many cases of prime and aged adults from the standpoint of geriatrics. Several of the well known deseases of such a type are, for example, myocardinal infarction, cerebral thrombosis, syndrome of disseminated intravascular coagulation and the like and, as is well known, urokinase of man origin and streptokinase are used as a therapeutic medicament therefor.
These medicaments are, however, not quite satisfactory in several respects. For example, urokinase of man origin is prepared from human urine as the starting material so that the supply thereof is limited by the availability of this starting material in large volumes. Streptokinase is defective due to the antigenicity. In addition, both of these medicaments must be used by instillation so that the patient under treatment suffers great pains unavoidably.
Therefore, it has been long desired to develop a novel fibrinolytically active agent usable as a therapeutic medicament of the above mentioned deseases without the problems in the conventional medicaments therefor. That is, one of the recent problems in the pharmaceutics has been to develop a novel fibrinolytically active agent free from the limitation by the availability of the starting material in large quantities and capable of being administrated to the patient not by the instillation but by other means, desirably orally, without giving pains to the patient.